The influence of the exocrine pancreatic secretions on development of small intestinal injury following localized hyperthermia was studied. In male Holtzman rats the excretory pancreatic ducts were occluded with metal hemostatic clips. An intraperitoneal injection of [3H]thymidine was given 3 weeks later. Three or 48 h after the injection a 10 cm segment of small intestine was exteriorized through a midline abdominal incision and heated at 38.0 degrees C, 42.5 degrees C, or 43.5 degrees C for 45 min. Intestinal damage was assessed 24 h after hyperthermia. The following four endpoints were used: histopathological injury score, the number of villi per intestinal circumference, the number of labelled epithelial cells in fixed areas of autoradiographic specimens, and incorporation of [3H]thymidine as determined by liquid scintillation counting. The correlation of results among the four methods of assessment was highly significant. The autoradiography data showed better correlation with both morphological parameters than the results of liquid scintillation counting. There was significantly less damage in heated segments from pancreatic duct-occluded animals than in segments from sham-operated controls. When hyperthermic injury was assessed morphologically the protection conferred by pancreatic duct occlusion was equivalent to lowering the temperature of heating by 1 degree C. It is concluded that morphological criteria may be superior to endpoints based on [3H]thymidine incorporation for assessment of hyperthermic injury in rat small intestine. Reducing the intraluminal pancreatic secretions appears to confer significant protection from small bowel injury after localized hyperthermia.